PXD043301

PXD043301 is an original dataset announced via ProteomeXchange.

Title	GPATCH4 regulates rRNA and snRNA 2’-O-methylation in both DHX15-dependent and DHX15-independent mannersGPATCH4 regulates rRNA and snRNA 2’-O-methylation in both DHX15-dependent and DHX15-independent manners
Description	Regulation of RNA helicase activity, often accomplished by protein cofactors, is essential to ensure target specify within the complex cellular environment. The largest family of RNA helicase cofactors are the G-patch proteins, but the cognate RNA helicases and cellular functions of numerous human G-patch proteins remain elusive. Here, we discover that GPATCH4 is a stimulatory cofactor of DHX15 that interacts with the helicase in the nucleolus via residues in its G-patch domain. We reveal that GPATCH4 associates with pre-ribosomal particles, and crosslinks to the transcribed ribosomal DNA locus and precursor ribosomal RNAs as well as binding to small nucleolar- and small Cajal body-associated- RNAs that guide rRNA and snRNA modifications. Global analysis of rRNA and snRNA 2’-O-methylation revealed that lack of GPATCH4 impairs methylation at various sites. We further demonstrated that the regulation of 2’-O-methylation by GPATCH4 is both dependent on, and independent of, its interaction with DHX15. Intriguingly, the ATPase activity of DHX15 is necessary for efficient methylation of DHX15-dependent sites, suggesting a function of DHX15 in regulating snoRNA-guided 2’-O-methylation of rRNA that requires activation by GPATCH4. Overall, our findings extend knowledge on RNA helicase regulation by G-patch proteins and also provide important new insights into the mechanisms regulating installation of rRNA and snRNA modifications, which are essential for ribosome function and pre-mRNA splicing.
HostingRepository	PRIDE
AnnounceDate	2025-08-15
AnnouncementXML	Submission_2025-08-15_04:17:43.853.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Aleksandar Chernev
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-26 04:55:46	ID requested
⏵ 1	2025-08-15 04:17:44	announced

10.1093/NAR/GKAD1202;

submitter keyword: small nucleolar RNA,RNA-protein crosslinking, RNA modification, 2’-O-methylation, ribosome, ribosome biogenesis, RNA helicase

Henning Urlaub
contact affiliation	Max-Planck-Institute for Multidisciplinary Sciences Bioanalytical Mass Spectrometry Group Am Fassberg 11 D-37077 Goettingen, Germany University Medical Center Goettingen Bioanalytics Institute for Clinical Chemistry Robert Koch Strasse 40 D-37075 Goettingen, Germany
contact email	henning.urlaub@mpinat.mpg.de
lab head
Aleksandar Chernev
contact affiliation	MPIbpc
contact email	aleksandar.chernev@mpibpc.mpg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD043301
     1. Label: PRIDE project
     2. Name: GPATCH4 regulates rRNA and snRNA 2’-O-methylation in both DHX15-dependent and DHX15-independent mannersGPATCH4 regulates rRNA and snRNA 2’-O-methylation in both DHX15-dependent and DHX15-independent manners